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Enhanced neointima formation following arterial injury in immune deficient Rag-1-/- mice is attenuated by adoptive transfer of CD8 T cells.

Dimayuga PC, Chyu KY, Kirzner J, Yano J, Zhao X, Zhou J, Shah PK, Cercek B - PLoS ONE (2011)

Bottom Line: Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased.CD4(+) T cell transfer did not reduce neointima formation.The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America. DimayugaP@cshs.org

ABSTRACT
T cells modulate neointima formation after arterial injury but the specific T cell population that is activated in response to arterial injury remains unknown. The objective of the study was to identify the T cell populations that are activated and modulate neointimal thickening after arterial injury in mice. Arterial injury in wild type C57Bl6 mice resulted in T cell activation characterized by increased CD4(+)CD44(hi) and CD8(+)CD44(hi) T cells in the lymph nodes and spleens. Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased. Adoptive cell transfer of CD4(+) or CD8(+) T cells from donor CD8-/- or CD4-/- mice, respectively, to immune-deficient Rag-1-/- mice was performed to determine the T cell subtype that inhibits neointima formation after arterial injury. Rag-1-/- mice that received CD8(+) T cells had significantly reduced neointima formation compared with Rag-1-/- mice without cell transfer. CD4(+) T cell transfer did not reduce neointima formation. CD8(+) T cells from CD4-/- mice had cytotoxic activity against syngeneic smooth muscle cells in vitro. The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

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CD8b+ cells in the injured artery of recipient Rag-1−/− mice.Detection of CD8b+ cells (A; reddish-brown stain) in arteries of recipient Rag-1−/− mice 21 days after injury. Adjacent sections double-stained (B) for CD8b+ (orange arrow) and active caspase-3 (dark blue stain, black arrowhead) showed positive cells in close proximity. Omission of primary antibodies was used as control (C). 1000× magnification.
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pone-0020214-g005: CD8b+ cells in the injured artery of recipient Rag-1−/− mice.Detection of CD8b+ cells (A; reddish-brown stain) in arteries of recipient Rag-1−/− mice 21 days after injury. Adjacent sections double-stained (B) for CD8b+ (orange arrow) and active caspase-3 (dark blue stain, black arrowhead) showed positive cells in close proximity. Omission of primary antibodies was used as control (C). 1000× magnification.

Mentions: Immuno-histochemical staining showed presence of CD8b+ cells in the neointimal layer of Rag-1+CD8 mice (Fig. 5A). Staining of consecutive sections showed presence of CD8b+ cells in close proximity to active caspase-3 stain (Fig. 5B) suggesting cytotoxic activity of the CD8b+ T cells.


Enhanced neointima formation following arterial injury in immune deficient Rag-1-/- mice is attenuated by adoptive transfer of CD8 T cells.

Dimayuga PC, Chyu KY, Kirzner J, Yano J, Zhao X, Zhou J, Shah PK, Cercek B - PLoS ONE (2011)

CD8b+ cells in the injured artery of recipient Rag-1−/− mice.Detection of CD8b+ cells (A; reddish-brown stain) in arteries of recipient Rag-1−/− mice 21 days after injury. Adjacent sections double-stained (B) for CD8b+ (orange arrow) and active caspase-3 (dark blue stain, black arrowhead) showed positive cells in close proximity. Omission of primary antibodies was used as control (C). 1000× magnification.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101237&req=5

pone-0020214-g005: CD8b+ cells in the injured artery of recipient Rag-1−/− mice.Detection of CD8b+ cells (A; reddish-brown stain) in arteries of recipient Rag-1−/− mice 21 days after injury. Adjacent sections double-stained (B) for CD8b+ (orange arrow) and active caspase-3 (dark blue stain, black arrowhead) showed positive cells in close proximity. Omission of primary antibodies was used as control (C). 1000× magnification.
Mentions: Immuno-histochemical staining showed presence of CD8b+ cells in the neointimal layer of Rag-1+CD8 mice (Fig. 5A). Staining of consecutive sections showed presence of CD8b+ cells in close proximity to active caspase-3 stain (Fig. 5B) suggesting cytotoxic activity of the CD8b+ T cells.

Bottom Line: Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased.CD4(+) T cell transfer did not reduce neointima formation.The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America. DimayugaP@cshs.org

ABSTRACT
T cells modulate neointima formation after arterial injury but the specific T cell population that is activated in response to arterial injury remains unknown. The objective of the study was to identify the T cell populations that are activated and modulate neointimal thickening after arterial injury in mice. Arterial injury in wild type C57Bl6 mice resulted in T cell activation characterized by increased CD4(+)CD44(hi) and CD8(+)CD44(hi) T cells in the lymph nodes and spleens. Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased. Adoptive cell transfer of CD4(+) or CD8(+) T cells from donor CD8-/- or CD4-/- mice, respectively, to immune-deficient Rag-1-/- mice was performed to determine the T cell subtype that inhibits neointima formation after arterial injury. Rag-1-/- mice that received CD8(+) T cells had significantly reduced neointima formation compared with Rag-1-/- mice without cell transfer. CD4(+) T cell transfer did not reduce neointima formation. CD8(+) T cells from CD4-/- mice had cytotoxic activity against syngeneic smooth muscle cells in vitro. The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

Show MeSH
Related in: MedlinePlus